Epilepsy drug shows potential for Alzheimer’s treatment

Neurons passing electrical signalsA drug commonly used to treat epilepsy could help clear the plaques in the brain associated with Alzheimer’s disease, according to researchers at the University of Leeds. The plaques are known to lead to the progressive death of nerve cells in the brain linked to many forms of dementia.

Sodium valproate - which is marketed as the anti-seizure drug Epilim - has been shown by scientists at the University of Leeds to reactivate the body’s own defences against a small protein called amyloid beta peptide, which is the main component of the brain plaques characteristic in Alzheimer’s. Their work was funded by the Medical Research Council.

“The fact that we’ve been able to show that a well-established, safe and relatively inexpensive drug could help treat Alzheimer’s is an extremely exciting development,” says lead researcher Professor Tony Turner from the University’s Faculty of Biological Sciences. “We hope colleagues will be able to progress this research with clinical trials in the near future.”

Alzheimer’s disease is the most common form of dementia and has no cure. In the UK today there a half a million people living with Alzheimer’s – and this is likely to double within a generation unless new treatments are found.

Sodium valproate has been used for many years to suppress epileptic seizures and the many sufferers of epilepsy have been taking the drug for decades with few side effects.

The development of Alzheimer’s is widely believed to be caused by the gradual accumulation in the brain of amyloid-beta peptide which is toxic to nerve cells. This is thought to be caused by a key enzyme called neprilysin or NEP gradually switching off in later life. One of NEP’s roles is to clear the toxic peptide from the brain, and plaques begin to form as it gradually switches off, leading to the death of the brain’s nerve cells.

The research team examined changes in chromatin – the ‘packaging’ that genes are contained within - and surmised that these changes might be involved in switching off NEP. The team found clear differences (acetylation) in key proteins within the chromatin when they compared normal nerve cells against those that failed to produce NEP.

“From there it was relatively simple to stimulate the expression of NEP with sodium valproate, which was seen to prevent the acetylation,” says Professor Turner. “We were elated when we saw the results.”

Professor Tony Turner, together with former colleague Dr John Kenny, first discovered NEP in the brain. His current research team comprises Dr Nikolai Belyaev, Dr Natalia Nalivaeva and Natalia Makova.

The research is published online in EMBO Reports.

Further information
Jo Kelly, campuspr, tel 0113 258 9880, mob 07980 267756, email jokelly@campuspr.co.uk

Guy Dixon, University of Leeds press office, tel 0113 343 8299, email g.dixon@leeds.ac.uk

Notes to Editors
Tony Turner is Professor of Biochemistry in the Institute of Molecular and Cellular Biology and former Dean of the University of Leeds’ Faculty of Biological Sciences.

The Faculty of Biological Sciences at the University of Leeds is one of the largest in the UK, with over150 academic staff and over 400 postdoctoral fellows and postgraduate students. The Faculty has been awarded research grants totalling some £60M and funders include charities, research councils, the European Union and industry. Each of the major units in the Faculty has the highest Grade 5 rated research according to the last government (HEFCE) Research Assessment Exercise, denoting research of international standing. The Faculty is also consistently within the top three for funding from the government’s research councils, the BBSRC and NERC. www.fbs.leeds.ac.uk

The University of Leeds is one of the largest higher education institutions in the UK with more than 30,000 students from 130 countries. With a turnover of £450m, Leeds is one of the top ten research universities in the UK, and a member of the Russell Group of research-intensive universities.

The Medical Research Council supports the best scientific research to improve human health. Its work ranges from molecular level science to public health medicine and has led to pioneering discoveries in our understanding of the human body and the diseases which affect us all. www.mrc.ac.uk